It’s a slow day in Longevity Land so here are some sage words from AgingDoc1:
Best bets come with risk.
Everything comes with risk.
Choose your bets wisely, but don’t let the fear of risk alone deter you.
Look the problem or opportunity right in the eye, weigh the evidence, & make your choice.
No one else will for you, nor should it be any other way.
Very good, its about finding a good base in life to take different decisions. This reminds me of Aristotle.
In Aristotle’s famous study of character, a frequent theme is the fact that a virtue lies between two vices. The virtue of courage, for example, lies between the vices of rashness and cowardice. The coward has too much fear, or fear when he should have none. The rash person has too little fear and excessive confidence.
Source: Virtue Theory
For me Rapamycin is about courage 
I am not sure Rapamycin is about courage. All the evidence is that there is little risk from taking rapamycin in the longevity variant. We know of a number of problems which indicate that it should not be taken when infected or around an operation.
On the other hand there is a certainty of deterioriation without improved autophagy (which rapamycin provides).
Much that I do things which are novel I am actually quite a cautious person and I assess the up sides and down sides of any decision. The down sides for rapamycin are really quite low.
For me courage is about thinking that Rapamycin is not a risk free path. Everything has a risk and this is something that is good to take inconsideration. We don’t for example know the long term effects of taking weekly dosing for many decades and what risk it may cause for healthy people. This is something the physician Peter Attia has pointed out. We don’t know what happens when you combine Rapamycin with other different longevity interventions. This is something the rapamycin researcher Matt Kaeberlein and Brian Kennedy have pointed out. They have seen combinations which can lead to detrimental effects.
I don’t feel overconfident around taking Rapamycin in a way which makes me feel that I could for example skip taking blood tests or doing it without supervision of a physician. There are different risks and problems that can occur when people take Rapamycin and I think it’s good to try to minimize those risks in different ways. Especially because it’s still early days around Rapamycin research in the longevity field.
I absolutely agree with Kristen Kauppi about taking certain risk when taking Rapamycin. I am still not clear about the right, individual dose for each person, about the schedule. For example, Peter Diamandis takes Rapamycin 6 mg per day for 3 months and then takes a month off. Why?
Some people take a small dose daily 6 days a week and take a day off. Some take it daily.
Some take very high doses weekly or every 2 weeks. There are multiple variations and there is no good explanation for them. Many take Rapamycin with grape fruit juice or other CYP3A4 inhibitors to artificially increase the dose of Rapamycin. Very few complete regular tests for Rapamycin level.
I need help to decide on the right dosage to avoid side effects but have longevity benefits.
You said it yourself. That’s what many of us do, just keep adjusting the dose until you are just below the level of negative side effects. Watch your biomarkers, how do you feel, etc.
Not terribly scientific.
Yeah, but if you can point me to someone who has a “terribly scientific” answer please do.
What if the side effects instead of indicating too much, are indicating an adequate dose?
My best bets are people who are way smarter and in the loop than me, are taking Rapamycin as a longevity agent. Good enough for Peter Attia and Peter Thiel, good enough for me. Of course, one has to listen to own’s body too. So far, rapamycin has been good to me.
Where did you hear that he has on-and-off periods. I’m trying to document down all such data and share it with the rapamycin community. Do you have a link where he says this?
Regarding the dose regime, my approach is to find the one that I can tolerate with an acceptable side effect profile.I inspire from others dose regime and people’s experiences around them. I’m not the person who will be the first to try a totally different dose regime without any research and/or lots of anecdotal data. So I will try to keep my dose regime around 6mg/weekly which is my dose regime currently.
Interesting, is Peter Thiel taking rapamycin? Do you have any source on that?
Peter Diamandis, MD - Longevity Practices
He takes Rapamycin 6 mg once a week for 3 months and takes a month off. He does not explain the rational for this schedule.
Do you use Rapamycinj by itself or in combination with grapefruit and/or EVO? I think that the combination makes it more difficult finding the right dose unless checking Rapamycin level on a regular basis.
How do I know that the dose I can tolerate is sufficient for longevity? I see some people take 2 mg per week without side effects. It is possibly placebo, which may have some benefit also?!
“How do I know that the dose I can tolerate is sufficient for longevity?”
You don’t and neither does anyone else know. But, animal studies are promising in that even low doses prolong life.
As far as I know, animal studies did’t compare the effect of very small doses with high doses of Rapamycin for longevity.
Do you know of such studies?
Please, the dosages and studies have been discussed extensively in the threads. Please, just query the “dose studies” or “rapamycin dosage” in the query box at the top of the page.
It’s very hard to get funding to do studies of everything when there is no profit to hardly anybody, so this is not surprising. Sad, but not a surprise.
I can’t think of a study that shows harm from Rapa. I think it has been shown that you should have a break weekly or biweekly with a level low enough to prevent Mtor2 from coming down too, right? Several popular ways to accomplish this. Nothing proven.
I can testify that it does decrease inflammation because my elbow doesn’t hurt for the first few days after taking, later it does. I’m biweekly.
I’m going to take this opportunity to tell a story on my wife. Her dad’s yard, which she inherited had a big dead spot because we removed trees. It was prepared but not seeded because it was summer and not a good time to seed. Later, when the fall rains came she asked me about seeding. How much seed to use, do I need fertilizer, how much to rake etc… obviously not happy with the answers no matter what because I didn’t have the studies I suppose. I could see she wasn’t going to get it done. So I said “Most of this does not matter, but if you don’t seed it I promise it won’t come up.” She actually agreed with me on that point, but still didn’t get it done. It was too much uncertainty. Really just spreading the seed out thick enough and it would have grown.
I think it’s the same with Rapa. All of these methods will result in good things happening. Pay attention to your body. You’ll be better off than if you do nothing. I’ve been on it for 3 years and that’s my best guess. I’m a farmer, not a doctor.
Good Luck,
The yard example makes sense, but the amount of seeds is important: 2-3 seeds would not do the job even with the best fertilizer.
My question is about the minimal dose of Rapamycin which may be effective for our purpose? Is it 2 mg/week or is it more?
We have no idea, to be honest.
Here are the dose/response examples from the ITP mouse studies below, and you can see the the higher the dose, the longer the lifespan. But the issue is that these mice live in pathogen free environments, so if they have a suppressed immune system, its less likely to result in an infection that will kill them. We are not so lucky. So we have to balance the dosing with the increased risk of immune supression and infections.
| Sirolimus Dose |
Mouse mg/kg/day Dose |
Mouse: Blood/Sirolimus Level |
Human mg/kg/day Dose |
Dose for 60kg Human | Daily Dose adjusted for longer half-life (/4) |
|---|---|---|---|---|---|
| 4.7ppm | ∼2.24 | 3 to 4 ng/mL | 0.182 mg/kg | 10.92 mg | 2.73 mg |
| 14ppm | ~6.67 | 9-16 ng/mL | 0.542 mg/kg | 32.54 mg | 8.135 mg |
| 42ppm | ~20 | 23-80 ng/mL | 1.626 mg/kg | 97.56 mg | 24.39 mg |
| 126ppm | ~60 | 4.878 mg/kg | 292.68 mg | 73.17 mg | |
| 378ppm | ~180 | 45 to 1800 ng/mL | 14.634 mg/kg | 878.04 mg | 218 mg |
| Sirolimus Dose |
mg/kg/day Dose |
Blood/Sirolimus Level |
Male Median LS Increase | Female Median LS Increase | |
| 4.7ppm | ∼2.24 | 3 to 4 ng/mL | 3% | 16% | |
| 14ppm | ~6.67 | 9-16 ng/mL | 13% | 21% | |
| 42ppm | ~20 | 23-80 ng/mL | 23% | 26% |
Based on the FDA animal to human dosing conversion guide here.
Note: ½ life for sirolimus in mice is approx. 15 hours, vs. approx. 62 hours in humans. So, mice metabolize sirolimus approximately 4 times faster than humans.